Melanin-concentrating hormone receptor antagonism differentially attenuates nicotine experience-dependent locomotor behavior in female and male rats.

Nicotine is a significant public health concern because it is the primary pharmacological agent in tobacco use disorder. One neural system that has been implicated in the symptoms of several substance use disorders is the melanin-concentrating hormone (MCH) system. MCH regulates various motivated behaviors depending on sex, yet little is known of how this interaction affects experience with drugs of abuse, particularly nicotine. The goal of this study was to determine the effect of MCH receptor antagonism on experience-dependent nicotine-induced locomotion after chronic exposure, particularly on the expression of locomotor sensitization. Adult female and male Wistar rats were given saline then cumulative doses of nicotine (0.1, 0.32, 0.56, and 1.0 mg/kg) intraperitoneally to determine the acute effects of nicotine (day 1). Next, rats were treated with 1.0 mg/kg nicotine for 6 days, given an identical series of cumulative doses (day 8), and then kept in a drug-free state for 6 days. On day 15, rats were pretreated with vehicle or the MCH receptor antagonist GW803430 (10 or 30 mg/kg) before another series of cumulative doses to assess response to chronic nicotine. After vehicle, male rats increased nicotine locomotor activation from day 1 to day 15, and both sexes showed a sensitized response when normalized to saline. The lower dose of GW803430 decreased locomotion compared to vehicle in females, while the higher dose decreased locomotion in males. Both sexes showed nicotine dose-dependent effects of GW803430, strongest at lower doses of nicotine. Controlling for sex-based locomotor differences revealed that females are more sensitive to GW803430. The high dose of GW803430 also decreased saline locomotion in males. Together, the results of our study suggest that MCH is involved in the expression of nicotine locomotor sensitization, and that MCH regulates these nicotine behavioral symptoms differently across sex.

The effects of reward and frustration in patients with bipolar disorder: Evidence from a computerized task with non-contingent feedback.

BACKGROUND: Bipolar disorder (BD) is characterized by mood changes that implies alterations in reward sensitivity and frustration tolerance. This study examined the effects of monetary reward and frustration on attentional performance and on affective experience across mood states in BD. METHODS: An Affective Posner Task in which the nature of contingencies are divided in the three successive blocks (baseline condition, monetary reward and non-contingent feedback) was applied to BD individuals in their different episodes: mania (n = 30), depression (n = 30), and euthymia (n =  30) as well as to a group of healthy controls (n = 30). RESULTS: Monetary reward improved performance (in terms of faster response times) in the euthymic group and the control group, whereas it impaired performance in the manic group and has not significant effect in the depressed group. In addition, an increased interference of frustration on response accuracy was exhibited in the three groups of BD patients (including euthymia) compared with healthy controls. LIMITATIONS: Participants' affective experience was self-informed by a Likert scale, so the reliability of this measure can be undermined in symptomatic patients in terms of stability and objectivity. Although it was statistically controlled, at the time of testing, all BD patients were medicated. CONCLUSIONS: A dissociated effect of reward and frustration was found between symptomatic and euthymic states in BD: whereas the benefit from monetary reward is affected only during symptomatic episodes (i.e., a state), the notably increased interference of frustration is exhibited also during euthymia (i.e., a trait).

The effects of the non-contingent presentation of safety signals on the elimination of safety behaviors: An experimental comparison between individuals with low and high obsessive-compulsive profiles.

BACKGROUND AND OBJECTIVES: Safety behaviors, defined as engagement in avoidance within safe environments, are a key symptom of obsessive-compulsive and related disorders. They may interfere with daily functioning and as such their emission should be reduced. The purpose of the current study is to investigate the effects of the non-contingent presentation of safety signals (cues produced by safety behaviors) on reducing safety behaviors in participants self-reporting low and high OCD profiles. METHODS: In total, 32 participants were asked to play a game to gain points and avoid their loss. After having developed avoidance behavior, evidenced by maintaining all of their earned points, they were exposed to safe environments where no point loss was programmed. In Test 1, safety cues (blue bar) were produced contingent on performing safety behaviors. In Test 2, safety cues were presented continuously without any response requirement. RESULTS: Findings demonstrated that high OCD group displayed higher rates of safety behaviors than low OCD group. However, exposure to the non-contingent presentation of safety signals eliminated their emission in both groups. LIMITATIONS: Future studies need to evaluate the effects of different non-contingent schedules on the suppression of safety behaviors. CONCLUSIONS: These findings contribute to the literature by demonstrating that non-contingent introduction of safety signals eliminated safety behaviors completely, even in high OCD participants, who performed safety behavior at higher rates. Such a treatment protocol may ameliorate exposure therapy in which response prevention constitutes a key element and is generally associated with increased drop-out rates.

Electrophysiological brain indices of risk behavior modification induced by contingent feedback.

The main aim of this research was to study the effects of response feedback on risk behavior and the neural and cognitive mechanisms involved, as a function of the feedback contingency. Sixty drivers were randomly assigned to one of three feedback groups: contingent, non-contingent and no feedback. The participants' task consisted of braking or not when confronted with a set of risky driving situations, while their electroencephalographic activity was continuously recorded. We observed that contingent feedback, as opposed to non-contingent feedback, promoted changes in the response bias towards safer decisions. This behavioral modification implied a higher demand on cognitive control, reflected in a larger amplitude of the N400 component. Moreover, the contingent feedback, being predictable and entailing more informative value, gave rise to smaller SPN and larger FRN scores when compared with non-contingent feedback. Taken together, these findings provide a new and complex insight into the neurophysiological basis of the influence of feedback contingency on the processing of decision-making under risk. We suggest that response feedback, when contingent upon the risky behavior, appears to improve the functionality of the brain mechanisms involved in decision-making and can be a powerful tool for reducing the tendency to choose risky options in risk-prone individuals.

Contributions of prolonged contingent and non-contingent cocaine exposure to escalation of cocaine intake and glutamatergic gene expression.

Similar to the pattern observed in people with substance abuse disorders, laboratory animals will exhibit escalation of cocaine intake when the drug is available over prolonged periods of time. Here, we investigated the contribution of behavioral contingency of cocaine administration on escalation of cocaine intake and gene expression in the dorsal medial prefrontal cortex (dmPFC) in adult male rats. Rats were allowed to self-administer intravenous cocaine (0.25 mg/infusion) under either limited cocaine-(1 h/day), prolonged cocaine-(6 h/day), or limited cocaine-(1 h/day) plus yoked cocaine-access (5 h/day); a control group received access to saline (1 h/day). One day after the final self-administration session, the rats were euthanized and the dmPFC was removed for quantification of mRNA expression of critical glutamatergic signaling genes, Homer2, Grin1, and Dlg4, as these genes and brain region have been previously implicated in addiction, learning, and memory. All groups with cocaine-access showed escalated cocaine intake during the first 10 min of each daily session, and within the first 1 h of cocaine administration. Additionally, the limited-access + yoked group exhibited more non-reinforced lever responses during self-administration sessions than the other groups tested. Lastly, Homer2, Grin1, and Dlg4 mRNA were impacted by both duration and mode of cocaine exposure. Only prolonged-access rats exhibited increases in mRNA expression for Homer2, Grin1, and Dlg4 mRNA. Taken together, these findings indicate that both contingent and non-contingent "excessive" cocaine exposure supports escalation behavior, but the behavioral contingency of cocaine-access has distinct effects on the patterning of operant responsiveness and changes in mRNA expression.

Tolerance to rewarding brain electrical stimulation: Differential effects of contingent and non-contingent activation of parabrachial complex and lateral hypothalamus.

Electrical stimulation of the parabrachial complex and related insular cortex induces concurrent conditioned place preference (CPP) in a naloxone-dependent manner. Furthermore, repeated rewarding activation of these regions generates tolerance, i.e., a reduction of the reinforcing effect. This study examined the effects of contingent and non-contingent stimulation in a CPP task. In the former modality, the animals can voluntarily select areas of the maze and thereby determine whether or not they receive stimulation. In the non-contingent procedure, the animals passively receive the administration of the rewarding electrical current while confined in the preferred place. Tolerance to the rewarding stimulation was observed in the non-contingent procedure, in which the external lateral parabrachial subnucleus (LPBe) was stimulated in a behaviorally passive task, but not in the contingent procedure. In contrast, no tolerance was observed in the group receiving rewarding stimulation of the lateral hypothalamus after either contingent or non-contingent brain activation. These findings are discussed in terms of the rewarding effects induced after contingent or non-contingent administration of electrical or chemical rewarding agents.

A bout analysis of operant response disruption.

Operant behavior appears to be organized in bouts of responses, whose parameters are differentially sensitive to various manipulations. This study investigated potential differential effects of three forms of operant response disruption-extinction (EXT), non-contingent reinforcement (NCR), and prefeeding (PRE)-on response bouts. In Experiment 1, Wistar Kyoto rats (WKY) were trained on a tandem variable-time (VT) 120s fixed-ratio (FR) 5 schedule of reinforcement; after stability was established, their responding was disrupted for three sessions with one of the three disrupters (EXT, NCR, or PRE). In Experiment 2, Long Evans (LE) rats were trained on a tandem VT 240s FR 5 to stability, and their responding disrupted with EXT or NCR. In EXT and NCR, response rates declined significantly and progressively over the course of the session, primarily due to a declining bout-initiation rate in EXT, and to fewer responses per bout in NCR. In contrast, a session-wide drop in response rate was observed in PRE, primarily due to a reduction in bout-initiation rate at the start of the session. These findings suggest that each form of disruption differentially impacts dissociable aspects of behavior. Theories of behavioral persistence should account for these functional relations, which appear to be obscured in response rate measures.

Further evaluation of latency-based brief functional analysis methods: An evaluation of treatment utility.

OBJECTIVE: Objectives were to evaluate latency-based brief functional analysis (BFA) model for identifying functions of aberrant behavior and treatments generated based on the results of the latency-based brief functional analysis. METHODS: We conducted latency-based BFA, including contingency reversals, and function-based treatment evaluations, including non-contingent reinforcement (NCR) and differential reinforcement of alternative behavior (DRA) with three individuals with autism using single subject design methodology. RESULTS: Socially-mediated functions (attention; tangible) were indicated for two participants and an automatic function was identified for one participant. The treatments generated based on results of the BFA were effective at reducing aberrant behavior for all participants. CONCLUSIONS: Results provide additional support that latency-based BFA model has utility in (a) the identification of functions of aberrant behavior and (b) the generation of function-based treatments. These results suggest clinicians who encounter setting and client-specific constraints (e.g. time; severity of aberrant behavior) have additional flexibility in choosing assessment tools.